Dietary Choline Deficiency as a New Model to Study the Possible Role of Free Radicals in Acute Cell Injury and in Carcinogenesis

Abstract

Over the last few years, working with a diet that is devoid of choline and in methionine (CD) we have observed that when this diet is fed to rats, they develop not only fatty liver, but also hepatocellular necrosis and cancer. In the course of our investigation as to the mechanism of cancer development by a dietary deficiency without any added carcinogen, we found that early nuclear lipid peroxidation (1), DNA alteration (2) and cell proliferation are very common features in the liver. Free radical generation and DNA alteration in a proliferating organ has been proposed as the initiating event in the development of liver cancer (see Fig. 1). However, the nature of free radical generated and the nature of DNA alteration are not known.